Fred Hutchinson Cancer Research Center and University of Washington School of Medicine, Seattle Cancer Care Alliance, Seattle, WA 98109, USA.
Curr Opin Urol. 2013 May;23(3):201-7. doi: 10.1097/MOU.0b013e32835e2253.
Prior to 2010, docetaxel was the only treatment shown to prolong survival in metastatic castrate-resistant prostate cancer (CRPC). In the past 3 years, several therapeutic agents have demonstrated survival improvements for CRPC after the receipt of prior docetaxel, leading to multiple approvals by the US Food and Drug Administration.
The development of these novel agents, each with a distinct mechanism of action, is the fruition of sedulous preclinical research and well designed clinical trials. Cabazitaxel, a next generation taxane, was the first Food and Drug Administration-approved drug for the postdocetaxel setting. The recognition of sustained androgen dependence of CRPC has led to the identification of more potent and selective inhibitors of androgen synthesis and androgen-receptor signaling, such as abiraterone and enzalutamide, respectively. Radium-223, an α-emitting radionuclide still under regulatory review, recently showed a significant survival benefit for CRPC. Finally, sipuleucel-T, a form of immunotherapy, may benefit a subset of patients in the postdocetaxel setting.
Post-docetaxel management of CRPC has undergone a dramatic yet welcome paradigm change in the past 3 years. With multiple life-prolonging agents available, it now becomes imperative to coordinate how and when these new therapies should be used and sequenced to achieve optimal patient outcomes.
目的综述：在 2010 年之前，多西他赛是唯一被证明能延长转移性去势抵抗性前列腺癌（CRPC）患者生存时间的治疗药物。在过去 3 年中，一些治疗药物在接受多西他赛治疗后对 CRPC 患者的生存时间有改善作用，这导致美国食品和药物管理局（FDA）批准了多种药物。
最近的发现：这些新型药物的开发，每种药物都有不同的作用机制，是认真的临床前研究和精心设计的临床试验的成果。卡巴他赛是一种下一代紫杉烷类药物，是 FDA 批准的第一种用于多西他赛治疗后的药物。CRPC 持续依赖雄激素的认识导致了雄激素合成和雄激素受体信号更有效的和选择性抑制剂的鉴定，如阿比特龙和恩扎鲁胺。镭-223，一种正在接受监管审查的α发射放射性核素，最近显示出对 CRPC 有显著的生存获益。最后，sipuleucel-T，一种免疫疗法，可能对多西他赛治疗后的一部分患者有益。
总结：在过去的 3 年中，CRPC 的多西他赛治疗后管理发生了显著但可喜的范式转变。有多种可延长生命的药物可供选择，现在必须协调如何以及何时使用这些新疗法以及对其进行排序，以实现最佳的患者结局。
